ALL 17 million farmed mink in Denmark were put at risk of being slaughtered last week after the discovery that mutant forms of the coronavirus are spreading among the animals. The virus has already spread back to humans. Some reports suggest that at least one of the mutations makes the virus more dangerous, although the idea is highly disputed, and claims that it could hamper the development of a vaccine don’t yet stand up to scrutiny.
The call for culling has now been dropped, but the human-mink-human transmission chain demonstrates the real and present danger of what virologists call “reverse spillover” and “spillback”. The pandemic began with spillover of SARS-CoV-2, the virus that causes covid-19, from wildlife to humans. Reverse spillover means transmission from humans back into animals, both wild and domesticated. Spillback completes the circle, with the virus jumping back into humans again.
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Threat to wildlife
This cyclical transmission represents a threat to both wildlife and humans. “The risk of SARS-CoV-2 infecting novel wild species is concerning enough to warrant preventative measures,” says Alison Peel of the Griffith Wildlife Disease Ecology Group at Griffith University in Queensland, Australia. Anyone who is at risk of coming into close contact with wild animals should take precautions, she and others say: wear a mask, wash your hands and keep your distance.
SARS-CoV-2 is known to be a highly promiscuous virus. Research into its origins strongly suggests that it started life in horseshoe bats and may have passed through an intermediate host, possibly , en route to humans.
The virus’s closest human-infecting relatives are similarly unfussy about who they get cosy with. The original SARS virus, SARS-CoV, which caused an epidemic of severe respiratory disease in 2002 and 2003, is also thought to have evolved in horseshoe bats and probably jumped into another species, either palm civets or racoon dogs, before infecting humans. The coronavirus behind MERS also originally probably came from bats but jumped into humans from dromedaries.
This jumping between species makes it impossible to designate a given coronavirus as, say, a “bat virus” or “pangolin virus”, says Samuel Díaz-Muñoz at the University of California, Davis. “I have an issue with defining viruses by their host. As long as they can move in and do their thing, viruses don’t care.”
“As long as viruses can move in and do their thing, they don’t care what the host is”
This jumping around doesn’t stop once the virus has reached humans. Onward transmission of SARS-CoV-2 into non-human animals has already been documented not just with mink, but also pet cats and dogs, and tigers and lions at Bronx Zoo in New York. has also been confirmed and while there is no evidence yet of cat-to-human transmission, it cannot be ruled out. Even before the outbreak in mink farms in Denmark, workers at a Dutch mink farm were known to have been .
These animals are in the firing line due to their close proximity to humans, but wild animals are susceptible too. Lab experiments have shown that the virus can infect , as well as various rodents, monkeys, marmosets and tree shrews. Cell culture experiments and computer models of the molecular interaction between the virus’s spike protein, which it uses to gain entry into cells, and potential host cells have added dozens more mammal species to the at-risk list, at least in theory, as well as a few birds, reptiles and even fish. Some animals, however, appear to be immune and attempts to infect them have failed, including house mice, pigs and domesticated birds such as chickens and ducks.
Unsurprisingly given the central role they play in brewing up new coronaviruses, most research on reverse spillover has focused on bats. That is especially true in parts of the world where bats remain free of betacoronaviruses, the subgroup of coronaviruses to which SARS-CoV-2 belongs. That’s because these bats’ lack of prior exposure to similar viruses may make them uniquely susceptible.
“17m
The number of mink that were almost culled in Denmark”
One of these regions is the temperate zone of North America. This is home to 45 species of bat that occur nowhere else in the world and have had no contact with bats outside the Americas for tens of millions of years, as bats don’t migrate across the Atlantic or Pacific oceans. Despite extensive surveys, betacoronaviruses have never been detected in any of these bats.
That may be because they aren’t susceptible to betacoronaviruses, but that is extremely unlikely, according to a by Paul Cryan of the US Geological Survey and Kevin Olival of the , a non-profit group that researches emerging diseases.
Endangered bats
While North American bats don’t have betacoronaviruses, they are loaded with closely related alphacoronaviruses. Bats elsewhere readily carry both types.
The fear is that the North American bats will prove highly susceptible to SARS-CoV-2 and experience major mortality. At least eight and maybe as many as 14 of the 45 species are , and under increasing pressure from habitat loss and wind turbine strikes. Bat populations already weakened by a fungal disease called white nose syndrome could be wiped out by the virus.
Reverse spillover into bats is obviously bad for bats, but could be a problem for us, too. For one thing, bats provide useful ecosystem services, including pollination, seed dispersal and pest control, so losing bat populations would have a severe impact on nature and farming. It could also push the pandemic to become even more out of control than it already is. “Bats could become a reservoir source of infection for people,” says Peel, with the virus then potentially spilling back into people.
This would make getting on top of the virus that much harder, as infected bats could reignite under-control epidemics in the same way that arriving from abroad have done in New Zealand and elsewhere.
Bats could even become a crucible for a new deadly virus. In one possible scenario, SARS-CoV-2 mutates into SARS-CoV-3 as it passes from bat to bat in vast roosts where many different species are known to mingle and swap viruses. In another scenario, a process called recombination creates a . Recombination happens all the time in coronaviruses because their genome-replicating enzymes are prone to jump from one bit of an RNA strand to another, so if a cell is simultaneously infected with two different coronaviruses they can end up being mashed together. Bats commonly carry multiple coronaviruses at the same time and recombination is plausibly how SARS-CoV-2 . It is also possible for coronaviruses to , unrelated, viruses.
“Bats could become a reservoir source of coronavirus infection for people”
Reverse spillover requires a fairly implausible chain of events, but there is precedent for all of them. For one thing, there are documented cases of viruses naturally spilling over from humans into bats. In 2013, a group of researchers including Olival – or “virodiversity” – of a species of fruit bat called the Indian flying fox. They estimated 58 viruses in total, two – or possibly three – of which had a human origin. One of them was a coronavirus.
What’s more, , the common cold-causing HCoV-NL63, which probably also originated in a bat, is still capable of infecting lung cells cultured from the tricolored bat, one of those North American species.
Calculated risk
Spillback is theoretically possible (see “How humans and bats transmit to each other“). But is it likely? “Determining whether or not it is likely needs to take into account three main factors,” says Peel. “One, the covid-19 prevalence in the human population. Two, the contact rates between bats and infected people. Three, whether novel bats are susceptible to infection and able to transmit the infection to other bats.” The latter factor has the most uncertainty, she says, but preliminary work suggests this is possible. “So we must focus our attention on the first two factors to avoid exposure in the first place,” she says.
With all of this in mind, in April, the US Geological Survey and the US Fish and Wildlife Service convened an expert panel, including Peel, to try to put some numbers on the risk in the US.
Though working with very limited data, the panel for example, if a research scientist who was infected and shedding virus handled a little brown bat under current fieldwork protocols, it found there is a roughly 15 per cent chance of the bat getting infected. For each such reverse-spillover event, there is about a 33 per cent chance that the virus would become established in wild bat populations.
Using personal protective equipment such as masks, gloves and gowns would significantly reduce the risk, the panel concluded, though it noted that PPE for healthcare workers is in short supply in some places
In April, the International Union for Conservation of Nature (IUCN) recommended a suspension of all fieldwork involving interactions with bats. It has since rowed back from a total moratorium, but , such as wearing PPE, only handling bats when absolutely necessary and never blowing on a bat, which researchers often do to examine its skin.
The IUCN has also issued , bat guano harvesters and . In a nutshell, when possible, steer clear of bats.
Another country that has no experience of bat betacoronaviruses is Australia. “To date, there is no evidence of any SARS or MERS-like viruses in any Australian bat species,” says Peel.
In August, she and her colleagues carried out a risk assessment for
Australia’s 81 species of bat. It concluded that the risk of reverse spillover was low, but there were such high levels of uncertainty that it recommended that people who know they are going to come into contact with bats should take precautions.
Bat backlash
The assessment also concluded that although the risk of Australian bats being sickened or killed by the virus are low, they are vulnerable to a “bat backlash” from humans spooked by the virus. SARS-CoV-2 has already led to politicians calling for bat culls and people bats in Australia and . The report warns that one species in Australia, the spectacled flying fox, which provides ecosystem services including pollination and seed dispersal, could be driven to local extinction this way.
The wildlife threat doesn’t begin and end with bats. A recent by a team led by Fabian Leendertz at the Robert Koch Institute in Berlin concluded that a wide range of distantly related mammals are susceptible to SARS-CoV-2 (see “Mammals at risk“). Drawing on evidence from natural transmission, cell cultures and , the researchers drafted a list of almost 60 mammal species that are definitely, probably or possibly susceptible, ranging from gorillas and chimps to foxes, yaks, giant pandas and koalas. Even some whales, dolphins and seals may be able to catch it.
“Yes, I was surprised by that,” says Leendertz. However, he points out that seals or sea lions probably to the Americas long before Europeans arrived, “so it is not totally impossible to have spillover between marine mammals and terrestrial ones”.
“Reverse spillover is something we have to keep an eye on. If we can avoid it, we should”
Leendertz and his colleagues also recommended that anyone at risk of coming into close contact with a wild mammal should take some now-familiar precautions: physical distancing, wearing a face mask and gloves, and frequent hand washing. The list of people who need to take such precautions is a long one, including wildlife researchers and conservationists, managers of protected areas, foresters, pest controllers, employees or volunteers in wildlife rehabilitation centres and wildlife tourism, and wildlife tourists themselves.
The mink slaughter debate has brought the wider issues of reverse spillover and spillback into the public consciousness. How worried should we be?
“I think the risk is very small at the moment because we are the main reservoir of the virus and the main drivers of the pandemic,” says Leendertz. “But consider a scenario where we have been able to control the virus and push it out of certain regions. Then you have to start thinking about the risk of reintroduction into the human population from secondary reservoirs in wild species. Reverse spillover is something we have to keep an eye on. If we can avoid it, we should.”
The threats of reverse spillover and spillback are teaching us something profound. “We need to change our interface with nature,” says Leendertz. “Especially with wild animals.”
Mammals at risk
Almost 60 species of mammal have so far been found to be susceptible, or probably/possibly susceptible, to SARS-CoV-2, while others probably aren’t at risk. These include:
Susceptible
Domestic cat (Felis catus)
Domestic dog (Canis lupus familiaris)
Raccoon dog (Nyctereutes procyonoides)
Ferret (Mustela putorius furo)
Mink (Neovison vison)
Lion (Panthera leo)
Tiger (Panthera tigris)
Probably susceptible
Chimpanzee (Pan troglodytes)
Western lowland gorilla (Gorilla gorilla gorilla)
Sumatran orangutan (Pongo abelii)
Red fox (Vulpes vulpes)
Leopard (Panthera pardus)
Cougar (Puma concolor)
Possibly susceptible
Domestic cow (Bos taurus)
Domestic goat (Capra hircus)
Domestic sheep (Ovis aries)
Horse (Equus caballus)
Orca (Orcinus orca)
Long-finned pilot whale, pictured (Globicephala melas)
Probably not susceptible
Wild boar (Sus scrofa)
Black-capped squirrel monkey (Saimiri boliviensis boliviensis)
Sperm whale (Physeter catodon)
Tufted capuchin (Sapajus apella)
Brown rat (Rattus norvegicus)
Not susceptible
Western European house mouse (Mus musculus domesticus)
For a full list see: Mammal Review,
How humans and bats transmit to each other
Bats and humans come into close contact frequently enough for viruses to pass between them.
According to the US Centers for Disease Control and Prevention, between 1997 and 2006, 17 people in the US caught rabies from bats. Most of these people reported handling a bat after finding it in or around their house, and two were bitten. But in three cases, they had no recollection of a bat encounter.
Rabies cannot be passed from person to person directly, but with a highly transmissible virus like SARS-CoV-2, it could take just one encounter to start a fresh outbreak.
Humans come into contact with bats in many other ways, including research, pest control, wildlife rehabilitation, wildlife tourism, recreational caving and when investigating disease outbreaks. Another contact is during guano harvesting, which is an important source of income in many parts of the world.
To pass viruses from humans to bats, actual contact may not be necessary. Since the virus is shed in human faeces and may remain infective for days in water, bats and other wildlife could pick it up by drinking sewage-tainted water.
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